Pulmonary toxicity with combined modality therapy for limited stage small-cell lung cancer.

To assess the pulmonary toxicity of radiation therapy combined with chemotherapy v chemotherapy alone, we reviewed the clinical course of 80 patients with limited stage small-cell lung cancer treated in a randomized prospective trial. Life-threatening pulmonary toxicity, defined as bilateral pulmonary infiltrates extending beyond radiation ports with symptoms requiring hospital admission, developed in 11 patients (28%) receiving combined modality therapy and in two (5%) receiving chemotherapy alone. Eight of these 13 patients died from pulmonary complications with no clinical evidence of tumor in five. Pulmonary toxicity initially presented at a median of 63 days (range, 21 to 150 days) after the start of combined modality therapy and at a median of 217 days after chemotherapy alone. Biopsies obtained in 11 patients with severe toxicity revealed only interstitial fibrosis with no evidence of an infectious agent. Review of pretreatment parameters such as age, performance status, and radiation portal area failed to reveal any significant differences between patients with or without pulmonary complications. However, initial pulmonary function tests (PFTs) revealed a significantly lower vital capacity (P = .03) and forced expiratory volume (FEV/1.0 second) (P = .04) in patients with subsequent pulmonary complications. Pulmonary toxicity was significantly more common with combined modality therapy than with chemotherapy alone (P = .017) and worse than expected with radiotherapy alone. Six- or 12-month PFTs in completely responding patients revealed improvement within the chemotherapy alone group and no clear trend within the combined modality group. For the group treated with radiation therapy and chemotherapy, there was significantly less improvement after 6 or 12 months in the forced vital capacity (P less than .005) and FEV/1.0 second (P less than .005) than observed for the group treated with chemotherapy alone. Despite the increased incidence of pulmonary toxicity, overall survival favored the combined modality arm (P = .07). Enhanced local control and disease-free survival appeared to compensate for the initial increased pulmonary morbidity and mortality in the group with combined modality therapy.

Relation of effectiveness of intracoronary thrombolysis in acute myocardial infarction to systemic thrombolytic state.

Twenty-nine patients received intracoronary thrombolytic therapy for acute myocardial infarction 3.5 +/- 1.4 hours (mean +/- standard deviation) after the onset of pain. Ten patients received urokinase (UK) and 19 patients received streptokinase (SK). Laboratory variables of the coagulation system were measured before and immediately after therapy. When comparing patients in whom coronary artery recanalization occurred vs those in whom the artery remained occluded, those in whom recanalization was achieved had greater alterations in fibrinogen, prothrombin time, activated partial thromboplastin time, fibrin/fibrinogen degradation products and plasminogen by thrombolytic therapy than did those in whom recanalization was not achieved (p less than 0.05 for all variables). Euglobulin lysis time showed a similar but nonsignificant trend (p = 0.114). Patients who received SK showed markedly greater alterations in coagulation parameters than did patients treated with UK (p less than 0.05 for 5 of 6 variables measured) and had a much higher incidence of successful thrombolysis (74% for SK, 20% for UK). These data indicate that the development of a systemic fibrinolytic state contributes to success when using intracoronary thrombolytic agents in acute myocardial infarction. Rather than being considered an adverse effect of therapy, a systemic lytic state may serve as a reasonable clinical goal in attempting to produce thrombolysis.

Variable intrathoracic upper airway obstruction due to non-small cell lung cancer. Palliation using physiologic and mechanical stenting.

A 48-year-old woman with non-small cell lung cancer involving the mediastinum and producing extrinsic tracheal compression is presented. The patient failed to respond to all conventional therapy and presented with stridor and respiratory distress due to progressive airway obstruction. Continuous positive airway pressure (CPAP) by mask was used to physiologically stent the airway until a mechanical Silastic stent could be placed by tracheostomy.

Fiberoptic bronchoscopy for refractory cough.

Fiberoptic bronchoscopy (FB) has a low yield in the diagnosis of chronic cough (greater than 3 weeks) in unselected patients. We assessed the yield of FB for cough during a four-year period in patients with nonlocalizing chest roentgenograms who were refractory to diagnostic efforts and empiric bronchodilator or antitussive therapy. Seven (28 percent) of 25 patients undergoing FB for cough (of greater than 1,500 bronchoscopies) had diagnostic findings (broncholithiasis, two; tracheobronchopathia osteochondroplastica, two; and tuberculous bronchostenosis, laryngeal dyskinesia, and arytenoid polyp, one each). No tracheobronchial neoplasms were detected. Age greater than 50 years and female sex independently predicted positive results (p = 0.02 Fisher's exact test), while duration of cough (two to 240 months), airflow, and smoking status did not. When patients with prior pulmonary or extrathoracic neoplasms were excluded, seven (35 percent) of 20 studies were diagnostic. Diagnoses potentially could have been made by thoracic computed tomographic scanning in four patients and indirect laryngoscopy in two. Fiberoptic bronchoscopy has a respectable yield for diagnosis of refractory chronic cough and is a reasonable procedure in carefully selected patients.

Tracheal occlusion from an intrathoracic stomach.

A patient presented with recurrent respiratory failure following esophagectomy. Systematic evaluation detected a previously unreported process causing this problem. Simple therapeutic measures were effective once the diagnosis was established.

Pulmonary complications of combination therapy with cyclophosphamide and prednisone.

Oral cyclophosphamide and prednisone are standard treatment for some neoplasms and necrotizing systemic vasculitis and are advocated with increasing frequency for idiopathic interstitial lung disease. During a 15-month period, we observed four cases of acute respiratory failure from Pneumocystis carinii pneumonia (PCP) in patients treated with oral cyclophosphamide and prednisone. One patient each had polyarteritis nodosa, Wegener's granulomatosis, bronchiolitis obliterans with organizing pneumonia, and chronic lymphocytic leukemia with red blood cell aplasia. Hypoalbuminemia (serum albumin level less than 3.0 g/dl) and daily therapy were associated with increased risk for development of PCP (p less than 0.05). None of the patients had leukopenia (less than 3,500/cu mm) or neutropenia (less than 1,000/cumm) at diagnosis. All were negative for the human immunodeficiency virus. Patients receiving oral cyclophosphamide and prednisone may be at higher or increasing risk for PCP. A high index of suspicion and aggressive evaluation for opportunistic infection are needed in these patients; consideration for trimethoprim-sulfamethoxazole prophylaxis and development of more quantitative measures of immunosuppression are needed.

Successful treatment of acute humoral rejection in a heart transplant patient.

Eight months after undergoing orthotopic heart transplantation, a patient had hypotension and biventricular heart failure. Endomyocardial biopsy specimens showed a modest cellular infiltrate, predominantly of plasma cells, and progressive myocyte injury, suggesting a humoral rejection process. The patient was treated with Minnesota antilymphoblast globulin and aggressively with plasmapheresis, resulting in evidence of myocyte repair, improved hemodynamics, and long-term survival.

Pericardial tamponade and massive pleural effusion complicating orthotopic heart transplantation.

Pericardial and pleural effusions occur commonly after open cardiac procedures. However, the combination of tamponade and massive pleural effusion is not often observed. We present a case of such a patient who received an orthotopic heart transplant in a setting of previously diagnosed systemic sarcoidosis. Treatment ultimately required the creation of a pericardial window and chemical pleurodesis.

Hemoptysis: a manifestation of pulmonary disease confidently managed by military physicians.

Military physicians can confidently manage hemoptysis with a systematic approach and optimal timing of consultation. Begin with a thorough history, physical examination, and chest x-ray. In our series of 177 cases, a cause for hemoptysis was found in 78% of those with abnormal chest x-rays but in only 21% of those with normal chest x-rays. All 36 cases of bronchogenic carcinoma were associated with an abnormal chest x-ray. A normal chest x-ray was associated with no cause found for the hemoptysis (44 cases) or bronchitis (25 cases), with no carcinomas developing upon a 2-year follow-up. Hospitalization is indicated with excessive bleeding or to allay patient or physician) anxiety. Diagnostic bronchoscopy is usually indicated, especially to localize the bleeding in massive hemoptysis (greater than 600 cc per 24 hours) when surgery may be indicated. Prompt referral should be the rule with bleeding from a mycetoma, diffuse bronchiectasis, or with recurrent significant hemorrhage (greater than 200 cc). In an active-duty population, these instances are fortunately rare, and conservative management and elective referral are the norm.

Bone and gallium scanning in the evaluation of disseminated coccidioidomycosis.

Bone and gallium scans were performed on 79 patients to determine the presence and extent of disseminated coccidioidomycosis. Bone scans appeared to be more sensitive than skeletal radiographs or gallium scans in determining the extent of coccidioidal bone involvement. The gallium scan was useful only in the identification of coccidioidal tissue abscesses. All patients with clinical evidence suggestive of dissemination and all patients with poor prognostic factors who are to receive amphotericin B therapy should be evaluated with a bone scan.

Patients with multidrug-resistant tuberculosis with low CD4+ T cell counts have impaired Th1 responses.

Multidrug-resistant tuberculosis (MDRTB) has emerged as a challenging clinical problem in both HIV-infected and -uninfected individuals. In this study, immune responses from HIV-negative patients with MDRTB were compared with those of healthy purified protein derivative (PPD)-positive and PPD-negative individuals. These responses were characterized by measuring the proliferation and cytokine production from PBMCs stimulated in vitro with Mycobacterium tuberculosis, PPD, or mitogens. MDRTB patients with CD4 counts >500/microl stimulated in vitro with M. tuberculosis had similar immune responses (proliferation, IFN-gamma, and IL-2 production) as the PPD-positive and -negative controls. By contrast, MDRTB patients with CD4 counts <500/microl had markedly deficient immune responses to similar stimuli. In these patients, IFN-gamma production could be restored by adding IL-12 to the in vitro cultures. IL-12 also caused a striking increase in the amount of IFN-gamma produced from PBMCs of both PPD-positive and -negative controls. The role of endogenous IL-12 production was also studied. Addition of anti-IL-12 to cultures resulted in a two- to eightfold decrease in IFN-gamma production in response to PHA stimulation. Inhibition of IFN-gamma was also observed when cells were stimulated by M. tuberculosis and PPD. Using Staphylococcus aureus Cowan strain as a mitogenic stimulus, IL-12 p70 was produced in similar amounts in all groups tested. TNF-alpha production was also assessed from cells stimulated by M. tuberculosis. Addition of IL-12 to the cultures did not cause a significant enhancement of TNF-alpha production. Last, production of IL-10 and IL-4 in response to M. tuberculosis and PHA, respectively, was not significantly different among all groups tested. These results suggest that patients with MDRTB tuberculosis with CD4 T cell counts <500/microl have impaired IFN-gamma and IL-2 responses and might benefit by adjunctive IL-12 therapy.